The broad objectives of this project are to elucidate more fully the mechanisms of action of the spermatogonial stem cell population in the mammalian testis, and to identify those factors which regulate its behavior. This knowledge is of fundamental importance in male reproductive biology and since stem cell spermatogonia are endowed with the ultimate responsibility both to perpetuate the germ cell line and to furnish an uninterrupted supply of spermatozoa throughout adult life; the functions--and malfunctions--of this compartment create reverberating and escalating effects throughout the rest of the spermatogenic process. For this reason, our ability, on the one hand, to successfully and reversibly interrupt spermatogenesis for purposes of fertility control, or on the other hand, to intelligently intervene in many cases of infertility, must be predicated on an understanding of stem cell behavior. As a first step in achieving these long-range objectives we feel that it is essential to understand how spermatogonia behave before attempting to identify what regulates their activity. To this end, we have chosen to study morphological and kinetic responses of stem cell spermatogonia to several situations which present varying hormonal environments, but have the common feature of a numerically sparse populations of differentiating cells. Specifically, we shall use morphological, quantitative and radioautographic tools to investigate spermatogonial behavior: 1) during growth of the seminiferous epithelium in immature rats when the hormonal milieu is in a state of flux; 2) during repopulation of the irradiated mouse testis when the hormonal climate is nearly normal; and 3) following hypophysectomy in adult rats where hormones are absent. Results of these studies will form the baselines of subsequent experiments designed to identify the agents which regulate spermatogonial activity.